Vapor growth of GeTe single crystals in micro-gravity

The positive effects of micro-gravity on crystal growth and fundamental properties of the vapor transport reaction were established by analyzing the results of GeSe and GeTe vapor transport experiments performed on board Skylab. The analysis was based on a direct comparison of GeSe and GeTe crystals and of mass transport rate data obtained on earth and in space. For this purpose, a total of six transport experiments employing different concentrations of transport agent (GeI4) and two temperature gradients were performed during the Skylab 3 and 4 missions. Extensive ground-based studies demonstrated that the crystal morphology and the mass transport rates of the above systems are affected by the transport conditions, in particular by gravity-driven convection. The results demonstrate unambiguously a considerable improvement of the space crystals in terms of surface perfection, crystalline homogeneity and defect density. The observation of greater mass transport rates than expected in micro-gravity environment is of basic scientific and technological significance. This indicates that conventional transport models are incomplete and demonstrates that crystals of improved quality can be grown at reasonable rates by this technique in space. Results are of practical importance for the modification of crystal growth techniques on earth

Atom-wave diffraction between the Raman-Nath and the Bragg regime: Effective Rabi frequency, losses, and phase shifts

We present an analytic theory of the diffraction of (matter) waves by a lattice in the "quasi-Bragg" regime, by which we mean the transition region between the long-interaction Bragg and "channelling" regimes and the short-interaction Raman-Nath regime. The Schroedinger equation is solved by adiabatic expansion, using the conventional adiabatic approximation as a starting point, and re-inserting the result into the Schroedinger equation to yield a second order correction. Closed expressions for arbitrary pulse shapes and diffraction orders are obtained and the losses of the population to output states otherwise forbidden by the Bragg condition are derived. We consider the phase shift due to couplings of the desired output to these states that depends on the interaction strength and duration and show how these can be kept negligible by a choice of smooth (e.g., Gaussian) envelope functions even in situations that substantially violate the adiabaticity condition. We also give an efficient method for calculating the effective Rabi frequency (which is related to the eigenvalues of Mathieu functions) in the quasi-Bragg regime.Comment: Minor additions, more concise text. To appear in Phys. Rev. A. 20 pages, 10 figure

Niche inheritance: a cooperative pathway to enhance cancer cell fitness though ecosystem engineering

Cancer cells can be described as an invasive species that is able to establish itself in a new environment. The concept of niche construction can be utilized to describe the process by which cancer cells terraform their environment, thereby engineering an ecosystem that promotes the genetic fitness of the species. Ecological dispersion theory can then be utilized to describe and model the steps and barriers involved in a successful diaspora as the cancer cells leave the original host organ and migrate to new host organs to successfully establish a new metastatic community. These ecological concepts can be further utilized to define new diagnostic and therapeutic areas for lethal cancers.Comment: 8 pages, 1 Table, 4 Figure

Investigating the response of leaf area index to droughts in southern African vegetation using observations and model-simulations

In many regions of the world, frequent and continual dry spells are exacerbating drought conditions, which have severe impacts on vegetation biomes. Vegetation in southern Africa is among the most affected by drought. Here, we assessed the spatiotemporal characteristics of meteorological drought in southern Africa using the standardized precipitation evapotranspiration index (SPEI) over a 30-year period (1982–2011). The severity and the effects of droughts on vegetation productiveness were examined at different drought timescales (1- to 24-month timescales). In this study, we characterized vegetation using the leaf area index (LAI) after evaluating its relationship with the normalized difference vegetation index (NDVI). Correlating the LAI with the SPEI, we found that the LAI responds strongly (r=0.6) to drought over the central and southeastern parts of the region, with weaker impacts (r<0.4) over parts of Madagascar, Angola, and the western parts of South Africa. Furthermore, the latitudinal distribution of LAI responses to drought indicates a similar temporal pattern but different magnitudes across timescales. The results of the study also showed that the seasonal response across different southern African biomes varies in magnitude and occurs mostly at shorter to intermediate timescales. The semi-desert biome strongly correlates (r=0.95) to drought as characterized by the SPEI at a 6-month timescale in the MAM (March–May; summer) season, while the tropical forest biome shows the weakest response (r=0.35) at a 6-month timescale in the DJF (December–February; hot and rainy) season. In addition, we found that the spatial pattern of change of LAI and SPEI are mostly similar during extremely dry and wet years, with the highest anomaly observed in the dry year of 1991, and we found different temporal variability in global and regional responses across different biomes. We also examined how well an ensemble of state-of-the-art dynamic global vegetation models (DGVMs) simulate the LAI and its response to drought. The spatial and seasonal response of the LAI to drought is mostly overestimated in the DGVM multimodel ensemble compared to the response calculated for the observation-based data. The correlation coefficient values for the multimodel ensemble are as high as 0.76 (annual) over South Africa and 0.98 in the MAM season over the temperate grassland biome. Furthermore, the DGVM model ensemble shows positive biases (3 months or longer) in the simulation of spatial distribution of drought timescales and overestimates the seasonal distribution timescales. The results of this study highlight the areas to target for further development of DGVMs and can be used to improve the models' capability in simulating the drought–vegetation relationship

Characteristic patterns of inter- and intra-hemispheric metabolic connectivity in patients with stable and progressive mild cognitive impairment and Alzheimer's disease

The change in hypometabolism affects the regional links in the brain network. Here, to understand the underlying brain metabolic network deficits during the early stage and disease evolution of AD (Alzheimer disease), we applied correlation analysis to identify the metabolic connectivity patterns using 18F-FDG PET data for NC (normal control), sMCI (stable MCI), pMCI (progressive MCI) and AD, and explore the inter- and intra-hemispheric connectivity between anatomically-defined brain regions. Regions extracted from 90 anatomical structures were used to construct the matrix for measuring the inter- and intra-hemispheric connectivity. The brain connectivity patterns from the metabolic network show a decreasing trend of inter- and intra-hemispheric connections for NC, sMCI, pMCI and AD. Connection of temporal to the frontal or occipital regions is a characteristic pattern for conversion of NC to MCI, and the density of links in the parietal-occipital network is a differential pattern between sMCI and pMCI. The reduction pattern of inter and intra-hemispheric brain connectivity in the metabolic network depends on the disease stages, and is with a decreasing trend with respect to disease severity. Both frontal-occipital and parietal-occipital connectivity patterns in the metabolic network using 18F-FDG PET are the key feature for differentiating disease groups in AD

Local orientational order in the Stockmayer liquid

Phase behaviour of the Stockmayer fluid is studied with a method similar to the Monte-Carlo annealing scheme. We introduce a novel order parameter which is sensitive to the local co-orientation of the dipoles of particles in the fluid. We exhibit a phase diagram based on the behaviour of the order parameter in the density region 0.1 \leq {\rho}\ast \leq 0.32. Specifically, we observe and analyse a second order locally disordered fluid \rightarrow locally oriented fluid phase transition.Comment: 13 pages, 7 figure

Novel gallium(III) complexes transported by MDR1 P-glycoprotein: potential PET imaging agents for probing P-glycoprotein-mediated transport activity in vivo

AbstractBackground: Multidrug resistance (MDR) mediated by expression of MDR1 P-glycoprotein (Pgp) represents one of the best characterized barriers to chemotherapy in cancer patients. Positron emission tomography (PET) agents for analysis of Pgp-mediated drug transport activity in vivo would enable noninvasive assessment of chemotherapeutic regimens and MDR gene therapy.Results: Candidate Schiff-base phenolic gallium(III) complexes were synthesized from their heptadentate precursors and gallium(III)acetylacetonate. Crystal structures demonstrated a hexacoordinated central gallium with overall trans-pseudo-octahedral geometry. Radiolabeled 67Ga-complexes were obtained in high purity and screened in drug-sensitive (Pgp−) and MDR (Pgp+) tumor cells. Compared with control, lead compound 6 demonstrated antagonist-reversible 55-fold lower accumulation in Pgp-expressing MDR cells. Furthermore, compared with wild-type control, quantitative pharmacokinetic analysis showed markedly increased penetration and retention of 6 in brain and liver tissues of mdr1a/b(−/−) gene disrupted mice, correctly mapping Pgp-mediated transport activity at the capillary blood–brain barrier and hepatocellular biliary cannalicular surface in vivo.Conclusions: These results indicate that gallium(III) complex 6 is recognized by MDR1 Pgp as an avid transport substrate, thereby providing a useful scaffold to generate 68Ga radiopharmaceuticals for molecular imaging of Pgp transport activity in tumors and tissues in vivo using PET

Mapping genomic and transcriptomic alterations spatially in epithelial cells adjacent to human breast carcinoma.

Almost all genomic studies of breast cancer have focused on well-established tumours because it is technically challenging to study the earliest mutational events occurring in human breast epithelial cells. To address this we created a unique dataset of epithelial samples ductoscopically obtained from ducts leading to breast carcinomas and matched samples from ducts on the opposite side of the nipple. Here, we demonstrate that perturbations in mRNA abundance, with increasing proximity to tumour, cannot be explained by copy number aberrations. Rather, we find a possibility of field cancerization surrounding the primary tumour by constructing a classifier that evaluates where epithelial samples were obtained relative to a tumour (cross-validated micro-averaged AUC = 0.74). We implement a spectral co-clustering algorithm to define biclusters. Relating to over-represented bicluster pathways, we further validate two genes with tissue microarrays and in vitro experiments. We highlight evidence suggesting that bicluster perturbation occurs early in tumour development

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.Cell Death and Differentiation advance online publication, 12 June 2015; doi:10.1038/cdd.2015.81